One of the key areas of focus for diabetes research, for both type 1 and type 2, is regenerative therapies. The theory being that research could regenerate our own insulin producing beta cells from adult progenitor cells that already reside in the adult pancreas, instead of islet transplantation from a donor. Islet transplants from a donor nest in the liver, instead of pancreas and is not the best place for islets to live.
Billions of dollars are being invested in this area because pharma can look at drugs already on the market and redirect them for more use. Biomedical firms like it because it offers them the ability to avoid some of the FDA requirements for new drug clinical trials, thus getting a vital therapy to the marketplace much sooner. It is a win/win for industry and patients!
In the area of regeneration, there have been some standout studies that are genuinely unique by using new technology and some drugs currently on the market. This makes them a very compelling new approach to diabetes management or curative therapy initiative. One of them that caught my eye was CureDM. I have been watching them for five years, recently reached out to Dr. Claresa Levetan, MD, co-founder of CureDM to find out the scoop!
In effort to crystallize the type of work that CureDM has been involved in, let’s get into the basics:
Defining “Islet” and “Beta Cell”
To begin with a little history, regeneration of the pancreas has been known since the 1930s. Before insulin was readily available to everyone with type 1, some children had their pancreas surgically tied off to help with glucose control. But long term, tying off the pancreas could not ward off the autoimmune attack on the newly generated islet that lies within the pancreas.
Often the words “islet” and “beta cells” are used interchangeably, but islet is short for the Islet of Langerhans, which is a highly complex cell containing 5 types of cells, alpha, beta, delta, epsilon and PP cells. Each one of these cells secretes one or more hormones that are critical to maintaining glucose control. Insulin is made in the beta cells and is the most important hormone for sustaining life, but 5 other hormones made in the pancreas, glucagon, pancreatic polypeptide, amylin, somatostatin and ghrelin, are also important for fine-tuning glucose control. (One interesting point I learned through this interview is that the distribution and amount of these cells and hormones are different in mice than humans, thus the other hormones made by the pancreas may play a more important to humans than to mice. Thus, insulin alone, cannot restore normal glucose levels, nor does insulin address the underlying problem of too few completely functional islets.
Can we create new beta cells?
For those of living with diabetes the word that most catches our attention when listening to research is “beta cell”. Type 1 diabetes is defined as an auto immune attack on the beta cell that live within the Islet of Langerhans. When beta cells are destroyed, the other cells of the islet try to compensate, but ultimately there is aberrant function of amylin and glucagon from the alpha cells, as well as other islet hormones. So it is important to remember that beta cells are part of the islet, but the islet contains other important cells that rely on a functioning beta cells to maintain normal glucose levels.
Our bodies form almost all of the islet cells we will have for a lifetime during embryogenesis and during the first year of life. It is a rare case when an adult will form new islet cells. Despite that Islet cells are only 1-2 percent of the total mass of the pancreas, they use 20% of the blood delivered to the pancreas! Just as the smallest bit of yeast is crucial to making sure your batter bakes into bread, those tiny beta cells are the main ingredient necessary in producing stable blood sugar in the body!
A healthy body has an estimated 1-2 million islets. Within a type 1 diabetic body we suffer 90% loss of beta cells, which secrete insulin and amylin. For type 2 diabetes, there is a 50-80 % reduction in beta cells at the time of diagnosis.
In order for us to regenerate beta cells we need stem cells to come into action. There are many avenues in progress around stem cells for beta cell regeneration, but CureDM focused its research on a progenitor cell. Progenitor cells are like stem cells because like they can turn into a specific kind of cell.
In a nutshell, progenitor cells are akin to adult stem cells in that they share many of the same properties as adult stem cells. Progenitor cells primarily act as a repair system for the body. They replenish special cells, but also maintain blood, skin and intestinal tissue. Progenitor cells lay dormant until they are called upon to replace cells lost by normal cellular aging process. When the body has an injury, or damaged or dead cells, the progenitor cells are stimulated into action by other cells and convert into the cells that are being lost a higher rate. Pancreatic progenitor cells may be a key in forming whole new functional islets from ones on pancreas and offers a potential cure for both type 1 and 2 diabetes.
So this raises the question about the possibility of using progenitor cells to help replace lost beta cells and the accompanied cells within the islet for both type 1 and type 2 diabetes. Part 2 will be on CureDM’s novel therapy called HIP (Human Islet Peptide). Stay tuned!